Senile dementia (also known as Alzheimer's disease, AD) is a common central nervous system degenerative disease, patients suffer from recent memory disorders, followed by persistent intelligence recession, loss of judgment and reasoning ability, dyskinesia, etc. As early as in 1976, Davies et discovered the phenomenon of dysfunction and apoptosis in central neurons and synapses particularly those involved in cholinergic neurons in AD patients. With the development of molecular biology, genes associated with AD which have been discovered include APP (amyloid precursor protein), PS1 (presenilin-1), PS2 (presenilin-2), ApoE4 and Cytochrome oxidase I and II encoded by mitochondrial, etc. The main pathological changes of AD are a regional neuronal loss and brain tissue atrophy, a large number of amyloid plaques appeared, also known as senile plaques (SP) and deposition of neurofibritary tangles, surrounded by dystrophic neuritis, activated microglia and astrocytes. The degree of dementia of an AD patient is positively correlated with developing of amyloid plaques. The main component of senile plaques is β-amyloid peptide: Aβ42, having a molecular weight of about 4.2 KD and consisting of 39˜43 amino acid residues, being formed from amyloid precursor protein (APP), a complete APP is Type I transmembrane protein which may be hydrolyzed by α-secretase or β-secretase, then disintegrated in the extracellular domain to produce sAPPα(soluble APP)/sAPPβ and CTFα(C-terminal fragments)/CTFβ, and CTFα/CTFβ could be cut by γ-secretase to produce a series of Aβ and CTFγ with different molecular sizes, mostmutations of PS could result in an increased production of Aβ42 through their effect on γ-secretase (may be a component of γ-secretase).
As shown in the investigation for health-threatening epidemics, the degree of concern for AD has leapt to the front position in senile diseases, and AD becomes a disease with a high incidence threatening the life and health of the elderly only next to cardiovascular disease, cancer, brain death. Although scientists have studied AD for many years, this disease, the most commondementia, is still uncurable. Currently the drugs for AD on the market can only improve the symptoms of AD patients, slow but not prevent or reverse the progression of disease. Therefore, the development of new drugs aimed at the etiology of AD disease not new mechanisms of symptoms is still the key research directions of domestic and foreign pharmaceutical companies.
Aβ42 plays a key role in occurrence and development of AD, and the current further researches of metabolism and toxicity of Aβ42 provide a wide range of potential drug targets for the treatment of AD. In WO2012/103282, ZHONG Yi reported a preferred target for the treatment of Alzheimer's disease—the epidermal growth factor receptor (EGFR) screened by employing transgenic fruit flies and double transgenic mice. Inhibition of EGFR could improve the condition of early memory loss of transgenic fruit flies and miceinduced by Aβ42, the pharmacological activity screening data showed an effectiveness of EGFR inhibitors which have been used clinically (such as gefitinib, erlotinib, lapatinib, canertinib) and EGFR inhibitors being studied (such as EKB-569, CL-387785, HKI-272, BIBW 2992, HKI-357, ZD-6474, AEE 788, XL647, BMS-599626, IPI-504, 17-AAG, JKF-006, JKF-011, JKF-027, GJ-06, GJ-06-1, GJ-12, GJ-12-1) in the treatment of Aβ42-induced memory loss of transgenic fruit flies and double transgenic mice with expression of Aβ42. The patent screened three compounds JKF-006, JKF-011, JKF-027 with a preferable curative effect.

In the present invention, the structure of compounds JKF-006, JKF-027 disclosed in WO2012/103282 is modified to produce to a series of 3-furan-2-cyano-2-acrylamide derivatives, and some of these derivatives have anti-Alzheimer's disease activities significantly higher than those of compounds JKF-006, JKF-027 disclosed in WO2012/103282 and the difference is significant, discovered in the activity-screening study for transgenic fruit flies.